i(3)so3-galactosylceramide and Endometrial-Neoplasms

Topics: Aging; Cerebroside-Sulfatase; Endometrial Neoplasms; Endometrium; Female; Humans; Polyps; Progesterone; Sulfoglycosphingolipids

It is well known that a poorly differentiated endometrial adenocarcinoma shows more rapid progression and a worse response to therapy than a well-differentiated endometrial adenocarcinoma. Qualitative and quantitative changes of cell surface glycolipids occur during neoplastic transformation. Sulfatide is one of the sulfated glycolipids in the cell membrane that may have an important role in various functions such as cell adhesion. To examine the molecular background of the morphological and biological features of well-differentiated and poorly differentiated cancer, we measured the levels of lipids, especially glycolipids, in tumor tissues from patients with endometrial carcinoma.. We determined the composition of lipids and glycolipids in tumor tissues, investigated glycosyltransferase messenger RNA expression by the reverse transcription-polymerase chain reaction, and assessed the localization of galactosylceramide sulfotransferase (an enzyme involved in sulfatide biosynthesis) by immunohistochemical staining.. No significant differences were observed between well-differentiated and poorly differentiated cancer with respect to the levels of cholesterol ester, cholesterol, phospholipids, cholesterol sulfate, ceramides, neutral glycolipids of the globo series, and GM3 ganglioside. However, the amount of sulfatides in well-differentiated tumors was significantly greater than that in poorly differentiated tumors, which was confirmed by thin-layer chromatography and immunostaining with a monoclonal antisulfatide antibody. Altered expression of sulfatide was found to be secondary to a change of galactosylceramide sulfotransferase messenger RNA expression. Immunohistochemical staining revealed that galactosylceramide sulfotransferase expression was characteristically observed in glandular areas but not in solid areas.. These findings suggest that sulfatide contributes to the well-differentiated phenotype of endometrial adenocarcinoma and that it is being expressed in normal uterine endometrium at sites of gland formation during the luteal phase, as we have previously reported.

Topics: Adenocarcinoma; Cell Differentiation; Chromatography, Thin Layer; Endometrial Neoplasms; Female; Humans; Immunoenzyme Techniques; Neoplasm Grading; Prognosis; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sulfoglycosphingolipids; Sulfotransferases

Endometrium biopsic samples from women with cystic hyperplasia or adenocarcinoma were analysed by biochemical procedures to verify fluctuations in the acidic glycosphingolipid (sulphatide) concentration and arylsulphatase A (ASA) activity. Comparing the values of the considered parameters with those obtained in normal subjects, it was observed that ASA activity significantly increased in both pathologies; in contrast, sulphatide concentration underwent a non-significant decrease in hyperplasia and a statistically significant increase in neoplasia. The thin-layer chromatography (TLC) images revealed not only quantitative, but also qualitative differences in the lipid fractions. In fact, compared with controls, the sulphatides showed one more marked fraction in the neoplastic endometrium, and two fractions with different Rf values in the hyperplastic one. Moreover, two new unknown fractions also appeared in some subjects with cystic hyperplasia. The findings suggest the lipid metabolism undergoes considerable changes under the pathological conditions examined. The fluctuations observed, in particular, in the sulphatide concentration are believed to be related to changes in the biosynthetic and catabolic activities of the key enzymes directly involved in their metabolism, i.e. arylsulphatase A and sulphotransferase, which are regulated by sex hormones.

Topics: Adult; Aged; Cerebroside-Sulfatase; Chromatography, Thin Layer; Cysts; Endometrial Neoplasms; Endometrium; Female; Glycosphingolipids; Humans; Hydrogen-Ion Concentration; Hyperplasia; Middle Aged; Sulfoglycosphingolipids